Scientific Method —

Discussing the art of synthesis with one of the masters

We attended a seminar given by K.C. Nicolaou, a veteran of natural products …

K.C. Nicolaou has been a leader in the world of natural products synthesis for decades, having published over 600 research papers, filed 79 patents, and won nearly every major award in the field. Although he needs no introduction among synthetic chemists, the rest of the world is probably unaware of his contributions. Even though nearly all of us has benefited from the labors of synthetic chemists when we take an antibiotic or a pain killer, we rarely stop to think about who made that drug, or the steps involved.

All of this explains why, when Nicolaou gave a talk for the general public at the San Diego Science Expo, he began with the basics, explaining that synthetic chemists are a bit like Lego artists. In his words, "synthetic chemists take atoms, which are like small pieces of Legos, and put them together to make large, complex molecules."

This building process isn’t merely an intellectual game to Nicolaou; instead, he has always felt that "synthesis is an art" and "nature is the best teacher and inspiration." In natural products chemistry, "you take something from nature, like a chemical from a plant in the rainforest or a rock in the desert or a creature at the bottom of the sea and you modify it. Then you fine tune it some more and finally develop it into a drug."

The ideal drug would fit perfectly into the chemical reactions happening in our body. As Nicolaou puts it, "our bodies are a community of molecules that are acting in harmonious integration, and if anything goes wrong, we get sick."

Throughout his talk, Nicolaou connected chemistry discoveries with our daily routine, driving home the point that all aspects of our lives are influenced by the work of chemists. He also showed a great appreciation for the full story behind every chemical. From aspirin to vancomycin, every drug was accompanied by pictures of the original plant or organism from which it was isolated and by photos of the first chemists who worked on the synthesis. The audience appeared to follow his talk easily, and several kids left the seminar excitedly discussing how "it’s so cool to get antibiotics from moldy vegetables."

Following his seminar, I had the opportunity to speak with Nicolaou for a few minutes about his participation at the Science Festival and related public outreach efforts.

Nicolaou speaks with an aspiring scientist before the seminar.

Ars: What motivated you to come here and speak to young people about science? Why is outreach important to you?

Nicolaou: We need to motivate our young people to get into science and try the impossible. We cannot sit back. The science programs in China and Japan are gaining. I was in China just last week and saw amazing progress. Money and manpower are what they have, and their government is looking ahead 50 years in science and technology. We need to compete and do hard work. We cannot just want to have the biggest military power. Military power is an empty shell without science and technology.

Ars: What factors directed you to science? Did an event or a mentor inspire you to pursue chemistry?

Nicolaou: I got into science from a high school teacher. He was a very colorful and outgoing person. I admired him both as a person and scientist. He had a PhD and was a high school teacher. Can you believe that? Those years we had great teachers in Cyprus. Kids were motivated to learn and work hard. It all began with colorful illustrations and art. He showed chemistry that changed color and other visual changes. I wanted to know why it happened. I became motivated, and I was good at it, and if you are good at something, you do more of it. So I was lucky to find both my passion and my talent. Once you do that, you can move on and do anything.

Ars: You definitely have a lot of colorful diagrams, pictures, and illustrations in your presentation slides which came from your book, Molecules that Changed the World. Did you write that book to bridge a gap between synthetic chemists and the general public? It has been many years since you were a novice to chemistry; how did you go about it without getting trapped in science jargon and such?

Nicolaou: Yes. Well, the best people to write science are the scientists because we know it so well, but it takes time. Between teaching, doing research, and mentoring, how does one find time to do this? But I felt it was important to do, and I started almost 10 years ago on this project. It began by giving lectures to general audiences, where I had to make slides for people who haven’t had special training in chemistry and other science.

I realized the importance of this to education and to inspire young people. It’s also important to inform the public about the impact of chemistry and biology on all aspects of society. It took us a long time to do this, but in the end it was worth it. When people tell me that they enjoyed the book, or if young people tell me that they were inspired, I feel the rewards are enormous in the end.

Ars: Countless molecules have changed the world. How do you choose which examples to use when you give talks like this, and how did you pick for the book? Was picking the molecules the most difficult part?

Nicolaou: It was hard to narrow down on the molecules. So, we picked up the molecules that can tell stories and have the most impact on medicine, biology, chemistry, and other parts of society. The pictures were really the most difficult part. We had to search in museums and galleries and companies specializing in photographs. I also had to send people to take the pictures, and I took a lot of them myself. We made a lot of the diagrams ourselves, and I had two computer specialists to organize the pages. I also had to pay a lot of money for copyrights. It took more time to put the art together than the science.

At the end of our conversation, I remembered one particular anecdote from Nicolaou’s talk. It was about his role in the synthesis of Taxol, a drug used in chemotherapy for ovarian, breast, lung, and other cancers. In the early stages of drug development, it had to be isolated from the bark of Pacific yew, which killed the tree and upset many conservationalists. Thus, there was a race among synthetic chemists to make the drug through less destructive means.

Nicolaou was one of the first people to come up with a way to synthesize Taxol. While his method is a classic example of organic chemistry and earned him a lot of respect in academic circles, his work was somewhat overshadowed by that of Robert Holton in the world of chemical industry. Holton found a more efficient way to make Taxol from a chemical isolated from the needles of European yew.

Holton’s method only required the tree to be trimmed, leaving the tree healthy and alive. "The irony," Nicolaou said, "was that I walked by a European yew everyday when I was banging my head against the wall trying to make Taxol. I thought sometimes that I should take some of the needles or the little red berries and see what chemicals can be found. Then, see if there is something useful. I never did it!"

So, when I asked Nicolaou what advice he had for young scientists, he naturally said, "Never put off something that you can do today. You could miss a great discovery. When you have an idea, just do it!"

Yun Xie
Yun Xie / Yun Xie is a contributing science writer at Ars, where she covers the latest advancements in science and technology for Ars. She currently works in scientific communications, policy, and review. Emailreenxie@gmail.com//Twitter@yun_xie